研究者詳細 - 座間味　義人

論文 - 座間味　義人

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Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage. 国際誌

Toshihiko Yoshioka, Mitsuhiro Goda, Masaya Kanda, Sayuri Itobayashi, Yugo Sugimoto, Yuki Izawa-Ishizawa, Kenta Yagi, Fuka Aizawa, Koji Miyata, Takahiro Niimura, Hirofumi Hamano, Takumi Sakurada, Yoshito Zamami, Keisuke Ishizawa

Clinical and translational science 16 ( 11 ) 2369 - 2381 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin-induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin-induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin-induced toxicity. In the mouse model of cisplatin-induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin-treated and valproic acid-treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin-induced decrease in cell viability was significantly suppressed by co-treatment with valproic acid. Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidney by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.

DOI： 10.1111/cts.13638

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Evaluation of cardiovascular toxicity of the atezolizumab and bevacizumab combination

Takahiro Niimura, Mitsuhiro Goda, Koji Miyata, Jun Matsumoto, Toshihiko Yoshioka, Hirofumi Hamano, Fuka Aizawa, Kenta Yagi, Yuki Izawa-Ishizawa, Yoshito Zamami, Keisuke Ishizawa

Frontiers in Drug Safety and Regulation 2023年8月

掲載種別：研究論文（学術雑誌）

<jats:p><jats:bold>Introduction:</jats:bold> The combination of atezolizumab, an immune checkpoint inhibitor (ICI), and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is the first choice for systemic therapy in hepatocellular carcinoma. Immune-related cardiovascular toxicity—myocarditis and pericarditis—are known to occur during ICI treatment. By contrast, VEGF inhibitors (VEGFIs) cause cardiovascular complications such as hypertension and heart failure. Thus, different cardiovascular toxicities have been recognized for ICIs and VEGFIs, but the impact of their combination remains unclear. Here, we aimed to investigate the cardiovascular toxicity profile of atezolizumab in combination with bevacizumab using the World Health Organization adverse event reporting database—VigiBase.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We analyzed data included in VigiBase till December 2022. To evaluate the frequency of reports related to atezolizumab, bevacizumab, and their combinations for 21 adverse events, we calculated the reporting odds ratio and information component. Analyses of the fatality of various cardiovascular toxicities associated with the use of each drug were performed.</jats:p><jats:p><jats:bold>Results:</jats:bold> The database included 84,951, 10,595, and 2,092 reports of treatment with bevacizumab, atezolizumab, and their combination, respectively. The disproportionality signal of hypertension, arterial embolism and thrombosis, supraventricular tachyarrhythmias, heart failure, myocarditis, hemorrhage-related clinical events, venous embolism and thrombosis, cardiomyopathy, respiratory failure with combination regimen of atezolizumab and bevacizumab was detected. Signals of these adverse events were also detected treatment with either atezolizumab or bevacizumab alone. Venous embolism and thrombosis exhibited the highest fatality rate in the two drug combination (12.82%) relative to those of atezolizumab (6.19%) and bevacizumab (4.54%).</jats:p><jats:p><jats:bold>Discussion:</jats:bold> Cardiovascular toxicity, owing to the combination of atezolizumab and bevacizumab, was similar to that of each single agent, and no new safety concerns were observed. Caution should be exercised when combining the two drugs since the fatality rate of thromboembolism increases with combination treatment.</jats:p>

DOI： 10.3389/fdsfr.2023.1213771

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ためになる薬の話薬物相互作用腎不全の薬物相互作用

濱野裕章, 鍛治園誠, 西原茂樹, 村川公央, 座間味義人

岡山医学会雑誌 135 ( 2 ) 89 - 91 2023年8月

Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis. 査読国際誌

Tsukasa Higashionna, Keisaku Harada, Akinari Maruo, Takahiro Niimura, Elizabeth Tan, Quynh Thi Vu, Takayoshi Kawabata, Soichiro Ushio, Hirofumi Hamano, Makoto Kajizono, Yoshito Zamami, Keisuke Ishizawa, Ko Harada, Shiro Hinotsu, Mitsunobu R Kano, Hideharu Hagiya, Toshihiro Koyama

Cancers 15 ( 15 ) 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

DOI： 10.3390/cancers15153786

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Structural characterization of the optical isomers esomeprazole and omeprazole using the JADER and FAERS databases. 査読国際誌

Mami Neishi, Hirofumi Hamano, Takahiro Niimura, Masaya Denda, Kenta Yagi, Koji Miyata, Tsung-Jen Lin, Tsukasa Higashionna, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa, Hideki Nawa

Toxicology and applied pharmacology 475 116632 - 116632 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: It is unclear whether the s (-) form of esomeprazole (EPZ) has an improved safety profile when compared with its racemic form omeprazole (OPZ). We assessed the potential complications of these optical isomers when combined with cilostazol, clopidogrel, and prasugrel, which are frequently used concomitant medications. METHODS: Using two adverse event spontaneous reporting databases, Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS), adverse event names for hemorrhage, venous/arterial embolization, and thrombus were obtained from the Medical Dictionary for Regulatory Activities. Reported odds ratios were calculated using a 2 × 2 contingency table, and a signal was considered present if the lower limit of the 95% confidence interval was >1. RESULTS: In combination with cilostazol, a hemorrhagic signal for OPZ in JADER and arterial emboli and thrombus signals for EPZ were detected in both databases. In combination with clopidogrel, OPZ showed arterial emboli and thrombus signals in JADER and venous/arterial emboli and thrombus signals in FAERS, while EPZ displayed arterial emboli and thrombus signals in FAERS. In contrast, when in combination with prasugrel, there were no adverse event signals in either database. CONCLUSION: This study has confirmed using big data, that EPZ, the optical isomer and racemic form of omeprazole, has the beneficial characteristics of being less sensitive to CYP, as was intended by its design.

DOI： 10.1016/j.taap.2023.116632

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Global trends of seasonal influenza-associated mortality in 2001-2018: A longitudinal epidemiological study. 査読国際誌

Hideharu Hagiya, Yuka Osaki, Michio Yamamoto, Takahiro Niimura, Ko Harada, Tsukasa Higashionna, Hirofumi Hamano, Yoshito Zamami, Shiro Hinotsu, Toshihiro Koyama

The Journal of infection 87 ( 3 ) e54-e57 2023年6月

Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics. 査読国際誌

Satoru Mitsuboshi, Hirofumi Hamano, Takahiro Niimura, Aya F Ozaki, Pranav M Patel, Tsung-Jen Lin, Yuta Tanaka, Ikuya Kimura, Naohiro Iwata, Shoya Shiromizu, Masayuki Chuma, Toshihiro Koyama, Yoshihiro Yamanishi, Yasunari Kanda, Keisuke Ishizawa, Yoshito Zamami

International journal of cancer 153 ( 8 ) 1472 - 1476 2023年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.

DOI： 10.1002/ijc.34616

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A polo-like kinase inhibitor identified by computational repositioning attenuates pulmonary fibrosis. 査読国際誌

Takeshi Imakura, Seidai Sato, Kazuya Koyama, Hirohisa Ogawa, Takahiro Niimura, Kojin Murakami, Yuya Yamashita, Keiko Haji, Nobuhito Naito, Kozo Kagawa, Hiroshi Kawano, Yoshito Zamami, Keisuke Ishizawa, Yasuhiko Nishioka

Respiratory research 24 ( 1 ) 148 - 148 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with few effective therapeutic options. Recently, drug repositioning, which involves identifying novel therapeutic potentials for existing drugs, has been popularized as a new approach for the development of novel therapeutic reagents. However, this approach has not yet been fully utilized in the field of pulmonary fibrosis. METHODS: The present study identified novel therapeutic options for pulmonary fibrosis using a systematic computational approach for drug repositioning based on integration of public gene expression signatures of drug and diseases (in silico screening approach). RESULTS: Among the top compounds predicted to be therapeutic for IPF by the in silico approach, we selected BI2536, a polo-like kinase (PLK) 1/2 inhibitor, as a candidate for treating pulmonary fibrosis using an in silico analysis. However, BI2536 accelerated mortality and weight loss rate in an experimental mouse model of pulmonary fibrosis. Because immunofluorescence staining revealed that PLK1 expression was dominant in myofibroblasts while PLK2 expression was dominant in lung epithelial cells, we next focused on the anti-fibrotic effect of the selective PLK1 inhibitor GSK461364. Consequently, GSK461364 attenuated pulmonary fibrosis with acceptable mortality and weight loss in mice. CONCLUSIONS: These findings suggest that targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting lung fibroblast proliferation without affecting lung epithelial cells. In addition, while in silico screening is useful, it is essential to fully determine the biological activities of candidates by wet-lab validation studies.

DOI： 10.1186/s12931-023-02446-x

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Cardiovascular Toxicities Associated with Anaplastic Lymphoma Kinase Inhibitors: A Disproportionality Analysis of the WHO Pharmacovigilance Database (VigiBase). 査読国際誌

Takahiro Niimura, Koji Miyata, Hirofumi Hamano, Yuuki Nounin, Hiroto Unten, Masaki Yoshino, Satoru Mitsuboshi, Fuka Aizawa, Kenta Yagi, Toshihiro Koyama, Mitsuhiro Goda, Yasunari Kanda, Yuki Izawa-Ishizawa, Yoshito Zamami, Keisuke Ishizawa

Drug safety 46 ( 6 ) 545 - 552 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Recently, cases of cardiovascular toxicities, such as pericarditis, caused by anaplastic lymphoma kinase (ALK) inhibitors have been reported; however, whether these adverse events are common among all ALK inhibitors remains unclear. AIMS: This study aimed to clarify the cardiovascular toxicity profile of ALK inhibitors using an adverse event spontaneous report database. METHODS: We analyzed data from VigiBase, the WHO global database of individual safety reports, from its inception in 1968 to December 2021. We calculated the reporting odds ratio to evaluate the association between ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) and 21 cardiovascular adverse events. Time to onset of pericarditis from ALK inhibitor administration was analyzed. RESULTS: Of the 27,994,584 reports, 19,911 involved treatment with ALK inhibitors. Among the 21 cardiovascular toxicities, only pericarditis signals were detected with all five ALK inhibitors (crizotinib [reporting odds ratios (ROR), 4.7; 95% CI 3.63-6.15], ceritinib [ROR, 12.9; 95% CI 9.37-17.79], alectinib [ROR, 4.8; 95% CI 3.15-7.42], brigatinib [ROR, 3.5; 95% CI 1.33-9.46], and lorlatinib [ROR, 6.4; 95% CI 3.60-11.22]). For torsade de pointes/QT prolongation, signals were detected with crizotinib (ROR, 5.0; 95% CI 3.72-6.77) and ceritinib (ROR, 4.2; 95% CI 2.17-8.05), whereas for hypertension, they were identified only with brigatinib (ROR, 3.9; 95% CI 2.88-5.20), and for heart failure, they were detected with alectinib (ROR, 2.2; 95% CI 1.60-2.90), crizotinib (ROR, 2.1; 95% CI 1.72-2.48), and lorlatinib (ROR, 2.0; 95% CI 1.27-3.23). Regarding time-to-onset analysis from drug administration to adverse event reporting, for pericarditis, it ranged from 52.5 days for alectinib to 166.5 days for crizotinib. CONCLUSIONS: Systematic evaluation of ALK inhibitor-associated adverse events revealed differences in the cardiotoxicity profiles among ALK inhibitors. Understanding the differences in the cardiovascular toxicity profile of each ALK inhibitor will contribute to safe drug therapy when switching between ALK inhibitors.

DOI： 10.1007/s40264-023-01300-9

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ドキソルビシン誘発心筋障害の予防薬探索

西内栞, 合田光寛, 新村貴博, 生田賢治, 八木健太, 相澤風花, 濱野裕章, 座間味義人, 石澤啓介, 西内栞, 石澤有紀

四国医学雑誌 79 ( 1-2 ) 139 - 139 2023年6月

ドキソルビシン誘発心筋障害の予防薬探索

西内栞, 合田光寛, 新村貴博, 生田賢治, 八木健太, 相澤風花, 濱野裕章, 座間味義人, 石澤啓介, 西内栞, 石澤有紀

四国医学雑誌 79 ( 1-2 ) 139 - 139 2023年6月

ためになる薬の話薬物相互作用(56-抗不整脈薬の薬物相互作用)

村尾卓哉, 江角悟, 濱野裕章, 村川公央, 座間味義人

岡山医学会雑誌 135 ( 1 ) 39 - 42 2023年4月

Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases. 査読国際誌

Satoru Mitsuboshi, Hirofumi Hamano, Yurika Kuniki, Takahiro Niimura, Masayuki Chuma, Soichiro Ushio, Tsung-Jen Lin, Jun Matsumoto, Tatsuaki Takeda, Makoto Kajizono, Yoshito Zamami, Keisuke Ishizawa

The Annals of pharmacotherapy 57 ( 11 ) 10600280231156270 - 10600280231156270 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: It is unclear whether use of a proton pump inhibitors (PPIs) increases the risk of rhabdomyolysis. OBJECTIVE: To clarify whether use of PPIs increases the risk of rhabdomyolysis. METHODS: This cross-sectional study analyzed data entered into the Medical Data Vision (MDV) database in Japan and into the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). The MDV data were analyzed to evaluate the association between use of PPIs and rhabdomyolysis. Then, the FAERS data were analyzed to evaluate whether the risk of rhabdomyolysis was increased further when a statin or fibrate was used concomitantly with a PPI. In both analyses, histamine-2 receptor antagonist was set as a comparator because it is used to treat gastric disease. In the MDV analysis, Fisher's exact test and multiple logistic regression analysis were performed. In the FAERS analysis, a disproportionality analysis using Fisher's exact test and multiple logistic regression analysis were performed. RESULTS: Multiple logistic regression analysis of both databases showed a significant association between use of PPIs and an increased risk of rhabdomyolysis (odds ratio [OR] = 1.74-1.95, P ≤ 0.01). However, use of a histamine-2 receptor antagonist was not significantly associated with increased risk of rhabdomyolysis. In the sub-analysis of the FAERS data, use of a PPI did not increase the risk of rhabdomyolysis in patients receiving a statin. CONCLUSION AND RELEVANCE: The data in 2 separate databases consistently suggest that PPIs may increase the risk of rhabdomyolysis. The evidence for this association should be assessed in further drug safety studies.

DOI： 10.1177/10600280231156270

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Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study. 査読国際誌

Kenta Yagi, Akinori Maruo, Shunsuke Ishida, Fuka Aizawa, Soichiro Ushio, Satoshi Sakaguchi, Makoto Kajizono, Takahiro Niimura, Mitsuhiro Goda, Hirofumi Hamano, Yuki Izawa-Ishizawa, Yoshito Zamami, Keisuke Ishizawa

Clinical and experimental medicine 23 ( 6 ) 2799 - 2804 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Gastric acid secretion inhibitors such as proton pump inhibitors (PPIs) and vonoprazan may change the duration of treatment with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for cancer. However, there are no data on this prolongation effect. Here, we aimed to determine whether the use of PPIs or vonoprazan in patients with cancer receiving bevacizumab affected the duration of bevacizumab treatment. This observational study was conducted at two national university hospitals in Japan and involved 222 patients using oral PPIs (N = 190) or vonoprazan (N = 32) at the start of bevacizumab treatment between January 2015 and December 2018. Patients who received only one course of bevacizumab were excluded. The primary endpoint was the duration of bevacizumab treatment. The duration of bevacizumab treatment varied significantly between the PPI and vonoprazan groups. For cancer types other than colorectal cancer (breast, lung, brain, and ovarian cancers), the median duration of treatment was 217 days (p < 0.05) and was longer in the vonoprazan group than in the PPI group. However, for colorectal cancer, the median duration of bevacizumab treatment was 147 days longer in the PPI group than in the vonoprazan group. Selection of appropriate gastric acid secretion inhibitors may improve the therapeutic efficacy of anti-VEGF drugs, including bevacizumab. Oestrogen is a key regulator of this effect and may be responsible for the varying association between PPI or vonoprazan administration and the difference in bevacizumab treatment duration between colon cancer and other cancer types.

DOI： 10.1007/s10238-023-01008-1

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Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma. 査読国際誌

Jun Matsumoto, Anzu Nishimoto, Shogo Watari, Hideo Ueki, Shoya Shiromizu, Naohiro Iwata, Tatsuaki Takeda, Soichiro Ushio, Makoto Kajizono, Masachika Fujiyoshi, Toshihiro Koyama, Motoo Araki, Koichiro Wada, Yoshito Zamami, Yasutomo Nasu, Noritaka Ariyoshi

Molecular and cellular biochemistry 478 ( 8 ) 1779 - 1790 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.

DOI： 10.1007/s11010-022-04637-4

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Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells. 査読国際誌

Rie Ando-Matsuoka, Kenta Yagi, Mayu Takaoka, Yuko Sakajiri, Tomokazu Shibata, Ryusuke Sawada, Akinori Maruo, Koji Miyata, Fuka Aizawa, Hirofumi Hamano, Takahiro Niimura, Yuki Izawa-Ishizawa, Mitsuhiro Goda, Satoshi Sakaguchi, Yoshito Zamami, Yoshihiro Yamanishi, Keisuke Ishizawa

Drug development research 84 ( 1 ) 75 - 83 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.

DOI： 10.1002/ddr.22013

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Characterization of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Using the United States Food and Drug Administration Adverse Event Reporting System. 国際誌

Takahiro Niimura, Yoshito Zamami, Koji Miyata, Takahisa Mikami, Mizuho Asada, Keijo Fukushima, Masaki Yoshino, Satoru Mitsuboshi, Naoto Okada, Hirofumi Hamano, Takumi Sakurada, Rie Matsuoka-Ando, Fuka Aizawa, Kenta Yagi, Mitsuhiro Goda, Masayuki Chuma, Toshihiro Koyama, Yuki Izawa-Ishizawa, Hiroaki Yanagawa, Hiromichi Fujino, Yoshihiro Yamanishi, Keisuke Ishizawa

Journal of clinical pharmacology 63 ( 4 ) 473 - 479 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICI). We assessed whether patient characteristics differed between those with immune checkpoint inhibitor-related MG and those with idiopathic MG. Reports from the United States Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of MG. Among 5,464,099 cases between 2011 to 2019, 53,447 were treated with ICIs. MG was reported more often in ICI user. Multiple logistic regression analyses showed that the reporting rate of ICI-related MG did not differ significantly between male and female; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95% confidence interval: 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related MG. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic MG, there was no sex difference in the development of ICI-related MG, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related MG more closely in older people. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jcph.2187

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大規模医療情報解析を活用したシスプラチン誘発急性腎障害に対する予防薬の探索

神田将哉, 合田光寛, 吉岡俊彦, 座間味義人, 石澤啓介, 小川敦, 石田俊介, 相澤風花, 新村貴博, 八木健太, 石澤有紀

四国医学雑誌 78 ( 5-6 ) 249 - 250 2022年12月

医療ビッグデータ解析と基礎研究を融合した研究手法によるハイブリッド創薬

合田光寛, 相澤風花, 八木健太, 新村貴博, 櫻田巧, 小川敦, 石澤有紀, 座間味義人, 石澤啓介

日本臨床薬理学会学術総会抄録集 43回 3 - 4 2022年12月

Polypharmacy in Older Adults with Alzheimer's Disease. 国際誌

Satoru Esumi, Soichiro Ushio, Yoshito Zamami

Medicina (Kaunas, Lithuania) 58 ( 10 ) 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The number of patients with Alzheimer's disease is increasing annually. Most of these patients are older adults with comorbid physical illnesses, which means that they are often treated with a combination of medications for the disease they have and those for Alzheimer's disease. Thus, older adults with Alzheimer's disease are potentially at risk for polypharmacy. In addition, the drug interactions between Alzheimer's disease medications and those for the treatment of physical illnesses may reduce their efficacy and increase side effects. This article reviews polypharmacy and drug interactions in elderly patients with Alzheimer's disease, with a focus on psychotropic drugs.

DOI： 10.3390/medicina58101445

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